Methionine is currently produced as a racemic mixture of DL-methionine by a well established chemical process. Most DL-methionine is being produced by variations of the same chemical procedure method involving toxic, dangerous, flammable, unstable, and highly odorous starting materials or intermediates. The starting materials for the chemical synthesis are: acrolein, methylmercaptan and hydrogen cyanide. The chemical synthesis involves the reaction of methylmercaptan and acrolein producing the intermediate 3-methylmercaptopropionaldehyde (MMP). In the further process the MMP reacts with hydrogen cyanide to form the 5-(2-methylthioethyl) hydantoin, which then can be hydrolyzed using 2 equivalents of caustics such as NaOH together with one half equivalent Na2CO3 to yield sodium-DL-methioninate and one equivalent Na2CO3 one equivalent NH3 and one half equivalent CO2. In the succeeding step the sodium-DL-methioninate is neutralized with 1.5 equiv. sulfuric acid and 1 equiv.Na2CO3 to yield DL-methionine Na2SO4 and CO2. It is obvious that such a chemical process yields a large molar excess of unused salts in comparison to the amount of methionine that is produced. This fact poses an economic and ecologic challenge.
Fermentative processes are usually based on cultivating microorganisms on nutrients including carbohydrate source (e.g., sugars such as glucose fructose or saccharose), nitrogen sources (e.g., ammonia) and sulfur sources (e.g., sulfate or thiosulfate) together with other necessary media components. The process yields only the natural product L-methionine and only biomass as a byproduct. Since no toxic, dangerous, flammable unstable, and highly odorous starting materials are being used and no salt is produced by a fermentative process, there is an advantage of this process over the chemical methionine synthesis. Methionine can be produced in organisms such as E. coli or Corynebacter (Kase H., Nakayama K. (1975) Agric. Biol. Chem. 39 pp 153-160; Chatterjee et al. (1999) Acta Biotechnol. 14, pp199-204; Harma S. Gomes, (2001) J. Eng. Life Sci. 1 pp. 69-73, JP 50031092, DE 2105189).
However, in all reported cases the yields for fermentatively produced methionine seem to be too low for an economic production. Therefore, an improved method is needed.